Diabetes mellitus is a serious disease that affects not only a patient's internal organs, circulation system and eyesight, but also a patient's lifestyle. There are reportedly more than 200 million diabetic people in the world at the moment, and this figure is expected to double within the next ten years. The first step in diabetes care is to monitor the patient's blood glucose level 24 hours a day, as knowing the glucose level assists in determining the right diet and medical treatment.
Current methods of measuring blood glucose concentrations typically require the diabetic patient to puncture a finger to collect a drop of blood, whose chemical composition is then analyzed by a glucose meter. As the procedure is not totally painless and harms the skin, diabetic patients are often unwilling to check their glucose level as frequently as their doctors prescribe, and are thus unable to sufficiently monitor their glucose level.
At present, the majority of portable devices for measuring glucose levels require puncturing the fingertip to obtain a blood sample. The blood sample is then placed on a test strip that indicates the glucose concentration. An example is the OneTouch® Ultra® glucose meter sold by LifeScan Inc., a Johnson & Johnson company. These devices are very compact and reasonably accurate, but puncturing the fingertip to obtain a blood sample is inconvenient and can be painful. Moreover, improper puncturing and hygiene may pose a risk of fingertip infection.
As an alternative to the traditional fingertip-puncturing methods, Cygnus Inc. has developed the GlucoWatch® Biographer monitor. The device, which looks like a wristwatch, pulls interstitial body fluid from the skin using small electric currents to extract glucose into a consumable transdermal pad, which acts as an iontophoretic sensor. The collected glucose triggers an electro-chemical reaction in the sensor, generating electrons. The sensor measures the electrons and equates the level of electron emission to a concentration of glucose in the body fluid. This device checks body fluid glucose levels every 20 minutes for up to 12 hours. Following the twelve hour period of operation, the monitor must be calibrated with a finger-prick reading for comparing with blood glucose levels. The device has a relative measuring error that has been determined to be approximately 10-30% in part because the glucose levels of interstitial fluid lags behind blood. However, in order to be able to even purchase one of these devices, a potential buyer must undergo and pass a physical and biochemical examination. Moreover, the device also has been known to severely inflame the skin in some patients with sensitive skin where the electrical currents are introduced.
Because of the lack of success of alternative devices such as GlucoWatch®, other non-invasive measurements have begun to be developed. Many of these alternative non-invasive methods involve using optical methods. Some of these optical methods have shown promise in providing a non-invasive measurement alternative. For example, some optical methods have used non-ionizing radiation to obtain a reading, providing fast responses without the need for consumable reagents. Moreover, as the availability of more sophisticated lasers and optical detectors increase, and the costs associated with using these optical devices decrease, optical methods may become an even more appealing alternative form of non-invasive measurement.
Typical non-invasive optical methods utilize a beam of light to irradiate some selected part of the human body, such as a finger, the forearm, tongue, lip, thigh or abdomen, etc. Light that is transmitted through, reflected, or scattered out of the skin comprises information about the composition of the irradiated tissue. This light is then received by optical detectors and analyzed to determine the concentrations of certain analytes, such as oxygen or hemoglobin. The analysis, however, is inherently complex because the received signal is often very faint and easily interfered with not only by a number of analytes in blood, but also by other factors including the variability and inhomogeneity of the human skin and the constantly changing human physiology, and even the external environment around the skin. Conventional optical methods of material analysis such as absorption and luminescent spectroscopy, Raman spectroscopy, and measuring polarization and reflectance changes are not sufficiently suitable for a turbid medium such as human tissue due to significant diffuse scattering of the reference light beam.
Other non-invasive methods take advantage of the correlation that exists between glucose content in the interstitial fluid and capillary blood, but suffer from the primary disadvantage of being time consuming. Furthermore, they only provide an indirect measure of glucose concentration, which is, unfortunately, also time-delayed.
The technique of laser photoacoustic spectroscopy has been used in trace detection due to the high sensitivity it offers. In the method of laser photoacoustic spectroscopy, a high-energy laser beam is used to irradiate the matter under study. The beam produces a thermal expansion in the matter, thereby generating an acoustic wave. The characteristics of the wave are determined not only by the optical absorption coefficient of the matter, but also by such thermal physical parameters as thermal expansion, specific heat, and sound velocity. In addition, the acoustic wave may also be affected by optical scattering, which influences the distribution of light in the matter that can be measured by high-sensitivity ultrasonic detectors such as piezo-electric crystals, microphones, optical fiber sensors, laser interferometers or diffraction sensors.
For example, U.S. Pat. Nos. 5,941,821 and 6,049,728 to Chou describe a method and apparatus for noninvasive measurement of blood glucose by photoacoustics. Upon irradiation, acoustic energy is generated in a relatively thin layer of the sample to be measured, characterized by a heat-diffusing length. The acoustic emission is detected with a differential microphone, one end of which is positioned in a measuring cell and the other end of which is positioned in a reference cell. A processor determines the concentration of the substance being measured based upon the detected acoustic signal. In order to determine the concentration of glucose in the bloodstream, the excitation source is preferably tuned to the absorption bands of glucose in spectral ranges from about 1520-1850 nm and about 2050-2340 nm to induce a strong photoacoustic emission. In these wavelength ranges, water absorption is relatively weak and glucose absorption is relatively strong.
As another example, U.S. Pat. No. 6,833,540 to MacKenzie, et al describes a system for measuring a biological parameter, such as blood glucose, the system directing laser pulses from a light guide into a body part consisting of soft tissue, such as the tip of a finger to produce a photoacoustic interaction. The resulting acoustic signal is detected by a transducer and analyzed to provide the desired parameter.
All of the above optical techniques are disadvantageous for at least the reason that they teach the application of energy to a medium without giving consideration to its acoustic oscillation properties, thus requiring relatively high laser power. Consequently, such techniques are energy inefficient, and provide an inadequate level of sensitivity.
Another prior art photoacoustic material analysis system is described in U.S. Pat. No. 6,466,806 to Geva, et al, in which the concentration of a component of interest in a medium is determined by resonant photoacoustic spectroscopy with a light pulse-train comprising equidistant short pulses having variable duration, frequency, number, and power. The light wavelength is selected so as to be absorbed by the component of interest. Upon irradiation, acoustic oscillations are generated by the absorbed light in a relatively thin layer of the medium, characterized by a heat-diffusing length. The frequency repetition of the short light pulses in the pulse-train is chosen to be equal to the natural acoustic oscillation frequency of the thin layer of the medium that can be considered as a thin membrane, such that the acoustic oscillation becomes resonant. Measuring of the amplitude and the frequency of the resonant oscillations determine the concentration of the component of interest, making the system suitable for monitoring of blood components, especially glucose.
Unfortunately, the above system, as well as the majority of prior art photoacoustic material analysis techniques, are disadvantageous. Contrary to the present invention, they teach the application of energy to a medium without giving consideration to the overlapping of absorption bands of different components, and the irregularity of elastic properties of a medium, such as human skin. Consequently, such prior art techniques provide an inadequate level of sensitivity and large errors of measuring.